Three species of biofilm-forming bacteria, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus, were recently identified by WHO as critical or high priority pathogens for which new antibiotics or antimicrobial treatments are urgently needed1. We believe the inability to effectively prevent or treat a wide range of biofilm-related chronic diseases may be overcome by using a biofilm dispersal signal as an adjunctive to conventional antimicrobial therapies. Studies in our laboratory have demonstrated that P. aeruginosa produces a quorum sensing molecule, cis-2-decenoic acid (cis-DA), that is responsible for auto- induction of the native dispersion response in biofilm bacteria. This signaling molecule has been shown to induce a physiological change in bacteria, causing them to disaggregate from a biofilm and alter their physiology, rendering them more susceptible to antibiotics. Additionally, cis-DA has been shown to induce biofilm dispersion in a wide range of Gram-negative and Gram-positive bacteria, as well as fungi. Here we propose to determine the degree to which cis-DA can improve the anti-biofilm activity of a petroleum jelly-based ointment with embedded antimicrobials (polymyxin B, bacitracin and neomycin). Experiments will examine the killing of pre- formed single- and multi-species biofilms. After confirming that the cis-DA adjunctive treatment is not toxic to human keratinocytes, we will test the effects on in vitro models of wounded and infected skin. In the final line of investigation, we will examine the efficacy and safety of the treatment in murine wound model. We anticipate that this work will result in an antimicrobial/anti-biofilm formulation that will improve current treatment and prevention strategies against biofilm infections in topical wounds.
The current proposal is a request for funding to begin the early-stage development of a novel adjunctive to antimicrobial treatment of biofilm infections caused by Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus; pathogens for which new, alternative antibiotic development has been identified as a critical or high priority. By stimulating the innate biofilm dispersion response, this adjunctive offers a unique and innovative antimicrobial strategy for enhancing the treatment of recalcitrant infections while generating minimal selective pressure for drug-resistance.
